AB0270 EFFECT OF METHOTREXATE USE ON JOINT AND LUNG DISEASE OUTCOMES IN PATIENTS HAVING RHEUMATOID ARTHRITIS WITH INTERSTITIAL LUNG DISEASE
Authors: M. Yoshida, T. Zoshima, M. Kawano
Journal: Annals of the Rheumatic Diseases (2022)

Background Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA). Although methotrexate (MTX) is an anchor drug for RA management, its use may worsen lung disease severity in patients with RA related ILD (RA-ILD). The safety and efficacy of MTX use in RA-ILD treatment have not been elucidated. Objectives We aimed to clarify the clinical characteristics of patients with RA-ILD and the effect of MTX use on joint and lung disease outcomes. Methods In this retrospective study, we included patients with RA-ILD who visited our department from 2011 to 2019 and underwent chest computed tomography (CT). RA was diagnosed using the 1987 ACR criteria or the 2010 ACR/EULAR classification criteria. During the abovementioned period, we defined the baseline as the time of the first chest CT scan; moreover, the final observation was defined as the time of the final chest CT scan in patients who underwent CT more than once, or as the final visit in those without a second chest CT scan. We excluded patients whose RA-ILD status could not be fully evaluated using chest CT scans due to other causes, including respiratory infections. Severe infections were defined as infectious events requiring hospitalization. To identify the clinical characteristics of patients with RA-ILD, we compared the features of RA with versus without ILD at baseline. To clarify the effect of MTX use on RA-ILD outcomes, we compared the outcomes of patients with RA-ILD with versus without MTX use. Furthermore, we investigated factors associated with RA disease activity or ILD deterioration using multivariate analyses. Results In this study, we included 452 patients (mean age, 60.2 years; females, 78.5%; mean observational period, 77.5 months), 325 (71.9%) of whom underwent chest CT more than two times. Patients with ILD (ILD; n=90, 19.9%) were older and had a higher RF positivity rate than those without ILD. Moreover, patients with ILD were treated with lower MTX use (20.2% vs. 52.9%, p&lt;0.001; 1.46 vs. 3.53 mg/week, p&lt;0.001) and TNF inhibitors exposure (21.1% vs. 13.1%, p&lt;0.044) than those without ILD, albeit with similar uses of prednisolone and other bDMARDs, including tocilizumab and abatacept. DAS28-CRP was higher in patients with than in those without ILD at baseline (4.60 vs. 3.42, p=0.063) and at the final observation (2.42 vs. 2.09, p=0.025). Linear regression analysis showed that baseline age and ILD were significantly associated with DAS28-CRP at the final observation (β=0.206 and 0.173, respectively). Kaplan Meier analysis revealed that patients with ILD experienced severe infections and respiratory infections more frequently than those without ILD (log-rank test, p&lt;0.001 and p&lt;0.001). Seventeen patients (20.2%) with ILD were treated with MTX. At baseline, these patients had similar ages and RF/ACPA positivity rates, as well as prednisolone and tDMARDs exposures, with higher bDMARD exposure (41.2 vs. 13.4%, p=0.016) compared to that in ILD patients without MTX use. DAS28-CRP was comparable in patients with and without MTX use at baseline, but was lower at the final observation in MTX-treated patients with ILD (1.41 vs. 2.73, p&lt;0.001). Kaplan Meier analyses revealed no differences in the frequencies of severe infections, respiratory infections, or ILD deterioration between patients with and without MTX use. Cox regression analysis demonstrated that the risk factors for ILD deterioration included baseline age (hazard ratio [HR] 1.088; 95% confidence interval [CI] 1.037-1.147), but not MTX use (HR 1.666; 95% CI 0.472-5.876). Conclusion RA-ILD were treated with lower MTX use, which resulted in higher RA disease activity. In contrast, patients with RA-ILD treated with MTX had lower RA disease activity without ILD deterioration. As RA-ILD is undertreated, appropriate MTX use may be required for effective RA-ILD treatment References [1]Arthritis Rheumatol 2021;73:1108-23. Disclosure of Interests None declared